Effect of timing of administration of first dose of antibiotics on clinical outcomes in children with septic shock

Abstract

Background : The surviving sepsis campaign guidelines advocates administration of first dose of antibiotics within the first hour of resuscitation in children with septic shock as the risk of mortality increases with every hour delay in administering antibiotics from the time of recognition of shock. There is a paucity of data on the adverse effects of delayed initiation of antibiotic therapy in children from resource restricted settings Methods : We conducted this prospective-cum-retrospective study from June 2013 to August 2017. Children aged 2 months to 17 years and admitted to pediatric intensive care unit (PICU) with septic shock but without prior antibiotic therapy were enrolled in the prospective cohort (Jan to Aug 2017) while records of such children admitted in PICU between 2013 and 2016 were reviewed for the retrospective cohort. The key clinical outcomes measured were duration of inotropic support, antibiotic therapy, mechanical ventilation, ICU stay and mortality. These outcomes were compared between children who received antibiotics after the first hour with those who received within the first hour of recognition of shock. Data was analyzed using Stata 11 Results : A total of 70 children were enrolled. Median (IQR) age was 2.8 (0.8, 6) years and males (66%) were in majority. Most common diagnosis was septicemia without focus (40%) followed by gastrointestinal sepsis (23%). Median (IQR) time lag between arrival at emergency room and recognition of shock was 5 minutes (0, 10) while median time lag between shock recognition and administration of first dose of antibiotics and first fluid bolus were 30 minutes (20, 52) and 15 minutes (5, 33) respectively. A total of 16 children died (22.9%). Fifteen children (22%) received antibiotics after the first hour (Group-1) while fifty-five (78%) received antibiotics within one hour of recognition of shock (Group-2). There was no difference in the age, admission diagnosis or PIM score between the two groups. Administration of first fluid bolus after shock recognition was delayed in group-1 (45 vs. 12 min; p=0.002). Fewer children in group-1 (57%) showed shock reversal by 6 hours of resuscitation when compared to group-2 (76%) but the difference was not significant (p=0.26). When compared to children in group-2, the following durations were significantly prolonged in group-1 children - antibiotic therapy (15 vs. 8 days; p=0.01), inotropic support (126 vs. 60 hours; p=0.01), mechanical ventilation (8 vs. 4 days; p=0.05) and PICU stay (13 vs. 4 days; p=0.01). There was no significant difference in mortality between the two groups - 2/14 (14%) vs. 15/56 (27%) (RR 0.53; 95% CI 0.14 to 2.06). Conclusion : Antibiotic administration within the 1st hour of recognition of septic shock seems to prolong the duration of antibiotic therapy, inotropic support and PICU stay in children with septic shock